{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:07:56Z","timestamp":1788052076437,"version":"build-2784847793"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    The developing forelimb has been a foundational model to understand how specified progenitor cells integrate genetic information to produce the tetrapod limb bauplan. Although the reigning hypothesis is that all tetrapods develop limbs in a similar manner, recent work suggests that urodeles have evolved a derived mode of limb dvelopment. Here, we demonstrate through pharmacological and genetic inactivation of\n                    <jats:italic>Sonic hedgehog<\/jats:italic>\n                    (\n                    <jats:italic>Shh<\/jats:italic>\n                    ) signaling in axolotls that\n                    <jats:italic>Shh<\/jats:italic>\n                    directs expansion and survival of limb progenitor cells in addition to patterning the limb across the proximodistal and antero-posterior axis. In contrast to inactivation of\n                    <jats:italic>Shh<\/jats:italic>\n                    in mouse or chick embryos where a humerus, radius, and single digit develop,\n                    <jats:italic>Shh<\/jats:italic>\n                    crispant axolotls completely lack forelimbs. In rescuing limb development by implanting SHH-N protein beads into the nascent limb field of\n                    <jats:italic>Shh<\/jats:italic>\n                    crispants, we show that the limb field is specified in the absence of\n                    <jats:italic>Shh<\/jats:italic>\n                    and that hedgehog pathway activation is required to initiate proximodistal outgrowth. When our results are examined alongside other derived aspects of salamander limb development and placed in a phylogenetic context, a new hypothesis emerges whereby the ability for cells at an amputation plane to activate morphogenesis and regenerate a limb may have evolved uniquely in urodeles.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2022.797352","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T04:57:00Z","timestamp":1648789020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Sonic hedgehog is Essential for Proximal-Distal Outgrowth of the Limb Bud in Salamanders"],"prefix":"10.3389","volume":"10","author":[{"given":"Sruthi","family":"Purushothaman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianda B.","family":"Lopez Avi\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley W.","family":"Seifert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1242\/dev.00191","article-title":"Tbx5 Is Essential for Forelimb Bud Initiation Following Patterning of the Limb Field in the Mouse Embryo","volume":"130","author":"Agarwal","year":"2003","journal-title":"Development"},{"key":"B2","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/nature00814","article-title":"T-box Gene Tbx5 Is Essential for Formation of the Pectoral Limb Bud","volume":"417","author":"Ahn","year":"2002","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"737","DOI":"10.6026\/97320630010737","article-title":"Molecular Docking Approaches in Identification of High Affinity Inhibitors of Human SMO Receptor","volume":"10","author":"Akare","year":"2014","journal-title":"Bioinformation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.ympev.2011.06.012","article-title":"A Large-Scale Phylogeny of Amphibia Including over 2800 Species, and a Revised Classification of Extant Frogs, Salamanders, and Caecilians","volume":"61","author":"Alexander Pyron","year":"2011","journal-title":"Mol. 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